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Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis.

Tornero-Esteban P, Rodríguez-Rodríguez L, Abásolo L, Tomé M, López-Romero P, Herranz E, González MA, Marco F, Moro E, Fernández-Gutiérrez B, Lamas JR - BMC Musculoskelet Disord (2015)

Bottom Line: Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis.To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation.We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. mptornero@gmail.com.

ABSTRACT

Background: The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs (miRNAs) during osteogenic differentiation of bone marrow MSCs from OA and healthy donors and to describe their possible implication in joint regeneration through modulation of molecular mechanisms involved in homeostatic control in OA pathophysiology.

Methods: Following phenotypic assessment of BM-MSCs obtained from OA diagnosed patients (n = 10) and non-OA (n = 10), total small RNA was isolated after osteogenic induction for 1, 10 and 21 days, miRNA profiles were generated using a commercial expression array of 754 well-characterized miRNAs. MiRNAs, with consistent differential expression were selected for further validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.

Results: A total of 246 miRNAs were differentially expressed (fold change ≥ ± 2, P ≤0.05) between OA and non-OA BM-MSC samples; these miRNAs showed variable interactions depending on the cell and differentiation status. Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis. In particular hsa-miR-335-5p, a critical regulator in bone homeostasis, was further studied. hsa-miR-335-5p downregulation in OA-MSCs, as well as their host coding gene, MEST, were also assessed.

Conclusions: To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation. We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features. These findings, may contribute to our understanding of the molecular mechanisms involved in MSCs mediated homeostatic control in OA pathophysiology that could be applicable in future therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus

Relative Quantification of comparisons between t = 10 and t = 0; t = 21 and t = 0 of significant miRNAs in OA-MSCs and Control-MSCs. Expression of miR210 and miR-335-5p follow a similar downregulation trend during osteogenic differentiation of MSCs, both in OA (n = 5) or in Control subjects (n = 3). Project was normalised using: hsa-miR-103a-3p; hsa-miR-191-5p; hsa-miR-30c-5p; SNORD49A. Test Type used: Parametric test (Limma). FDR method: Benjamini-Hochberg Adjusted p-value threshold: 0.05
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Fig2: Relative Quantification of comparisons between t = 10 and t = 0; t = 21 and t = 0 of significant miRNAs in OA-MSCs and Control-MSCs. Expression of miR210 and miR-335-5p follow a similar downregulation trend during osteogenic differentiation of MSCs, both in OA (n = 5) or in Control subjects (n = 3). Project was normalised using: hsa-miR-103a-3p; hsa-miR-191-5p; hsa-miR-30c-5p; SNORD49A. Test Type used: Parametric test (Limma). FDR method: Benjamini-Hochberg Adjusted p-value threshold: 0.05

Mentions: Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of the 21 used for validation showed a significative downregulated expression during osteogenesis. More specifically, hsa-miR-210 expression pattern was quite similar in OA and control MSCs, which is reflected by an average downregulation of 5.5 times between days [0–10] and 9.5 times between days [0–21]. A downregulatory trend also occurs during osteogenesis for miR-335-5p, which was down-regulated an average of 2 and 12 fold respectively, although not significant in the case of OA-MSCs (Fig. 2).Fig. 2


Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis.

Tornero-Esteban P, Rodríguez-Rodríguez L, Abásolo L, Tomé M, López-Romero P, Herranz E, González MA, Marco F, Moro E, Fernández-Gutiérrez B, Lamas JR - BMC Musculoskelet Disord (2015)

Relative Quantification of comparisons between t = 10 and t = 0; t = 21 and t = 0 of significant miRNAs in OA-MSCs and Control-MSCs. Expression of miR210 and miR-335-5p follow a similar downregulation trend during osteogenic differentiation of MSCs, both in OA (n = 5) or in Control subjects (n = 3). Project was normalised using: hsa-miR-103a-3p; hsa-miR-191-5p; hsa-miR-30c-5p; SNORD49A. Test Type used: Parametric test (Limma). FDR method: Benjamini-Hochberg Adjusted p-value threshold: 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4526194&req=5

Fig2: Relative Quantification of comparisons between t = 10 and t = 0; t = 21 and t = 0 of significant miRNAs in OA-MSCs and Control-MSCs. Expression of miR210 and miR-335-5p follow a similar downregulation trend during osteogenic differentiation of MSCs, both in OA (n = 5) or in Control subjects (n = 3). Project was normalised using: hsa-miR-103a-3p; hsa-miR-191-5p; hsa-miR-30c-5p; SNORD49A. Test Type used: Parametric test (Limma). FDR method: Benjamini-Hochberg Adjusted p-value threshold: 0.05
Mentions: Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of the 21 used for validation showed a significative downregulated expression during osteogenesis. More specifically, hsa-miR-210 expression pattern was quite similar in OA and control MSCs, which is reflected by an average downregulation of 5.5 times between days [0–10] and 9.5 times between days [0–21]. A downregulatory trend also occurs during osteogenesis for miR-335-5p, which was down-regulated an average of 2 and 12 fold respectively, although not significant in the case of OA-MSCs (Fig. 2).Fig. 2

Bottom Line: Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis.To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation.We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC). UGC de Reumatología, Hospital Clínico San Carlos, 4a Planta, Ala Norte. C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain. mptornero@gmail.com.

ABSTRACT

Background: The aim of this study was to evaluate, the existence of a signature of differentially expressed microRNAs (miRNAs) during osteogenic differentiation of bone marrow MSCs from OA and healthy donors and to describe their possible implication in joint regeneration through modulation of molecular mechanisms involved in homeostatic control in OA pathophysiology.

Methods: Following phenotypic assessment of BM-MSCs obtained from OA diagnosed patients (n = 10) and non-OA (n = 10), total small RNA was isolated after osteogenic induction for 1, 10 and 21 days, miRNA profiles were generated using a commercial expression array of 754 well-characterized miRNAs. MiRNAs, with consistent differential expression were selected for further validation by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis.

Results: A total of 246 miRNAs were differentially expressed (fold change ≥ ± 2, P ≤0.05) between OA and non-OA BM-MSC samples; these miRNAs showed variable interactions depending on the cell and differentiation status. Two miRNAs, hsa-miR-210 and hsa-miR-335-5p out of 21 used for validation showed a significant downregulated expression during induced osteogenesis. In particular hsa-miR-335-5p, a critical regulator in bone homeostasis, was further studied. hsa-miR-335-5p downregulation in OA-MSCs, as well as their host coding gene, MEST, were also assessed.

Conclusions: To our knowledge, this study represents the most comprehensive assessment to date of miRNA expression profiling in BM-MSCs from OA patients and their role during osteogenic differentiation. We describe the existence of a correlation between miR-335-5p expression and OA indicating the putative role of this miRNA in OA features. These findings, may contribute to our understanding of the molecular mechanisms involved in MSCs mediated homeostatic control in OA pathophysiology that could be applicable in future therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus